Studies on the effect of MDMA (‘ecstasy’) on the body temperature of rats housed at different ambient room temperatures

3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) administration to rats produces hyperthermia if they are housed in normal or warm ambient room temperature (Ta) conditions (20°C), but hypothermia when in cool conditions (Ta17°C). We have now investigated some of the mechanisms involved. MDMA (5 mg kg−1 i.p.) produced a rapid decrease in rectal temperature in rats at Ta 15°C. This response was blocked by pretreatment with the dopamine D2 receptor antagonist remoxipride (10 mg kg−1 i.p.), but unaltered by pretreatment with the D1 antagonist SCH23390 (1.1 mg kg−1 i.p.). MDMA (5 mg kg−1) did not alter the tail temperature of rats at Ta 15°C, but decreased the tail temperature of rats at Ta 30°C. A neurotoxic dose of MDMA (three doses of 5 mg kg−1 given 3 h apart) decreased cortical and hippocampal 5‐HT content by approximately 30% 7 days later. This lesion did not influence the rise in tail temperature when rats were moved from Ta 20°C to 30°C compared to nonlesioned controls, but did result in a lower tail temperature than that of controls when they were returned to Ta 24°C. Acute administration of MDMA (5 mg kg−1) to MDMA‐lesioned rats produced a sustained decrease in tail temperature in rats housed at Ta 30°C compared to nonlesioned controls. These data suggest that the thermoregulatory problems previously observed in MDMA‐lesioned rats housed at Ta 30°C result, partially, from their inability to lose heat by vasodilation of the tail, a major heat‐loss organ in this species. British Journal of Pharmacology (2005) 146, 306–312. doi: 10.1038/sj.bjp.0706318